The proposed research program is organized to examine, primarily by advanced electron microscope techniques, the cell biology of the alveolar-capillary unit of the lungs. Two of the component cells, namely the capillary endothelial cells and the type II alveolar epithelial cells appear to carry out specific metabolic activities and are independent of the physical exchange of gases between blood and air. The endothelial cells contain hydrolase enzymes capable of metabolizing circulating hormonal substances, inactivating some (e.g. gradykinin) while activating others (e.g. angiotensin I). Our previous studies indicate that the enzymes responsible for these metabolic events are situated on or very near the luminal surface of the endothelial cells. Using endothelial cells in situ and isolated in culture, we plan to coordinate biochemical and autoradiographic techniques further to examine the mechanisms by which endothelial cells process circualating hormones. Additionally, endothelial cells will be studied using freeze-fracture and etching techniques to clarify relationships between intramembranous particles and hydrolase enzymes and to define the nature of the intercellular junctions. Studies of type II alveolar cells will pursue results of our pilot study, which showed evidence of elaboration of tubular myelin on the surfaces of the lamellar body leaflets exposed by freeze-fracturing. Additionally, by coordinating EM studies of thin sections and freeze-fracture replicas along with the use of cytochemical techniques, we plan to examine the genesis, maturation and mode of release of lamellar inclusions. The overall objective of our research is to develop an improved understanding of the alveolar-capillary unit in its role in the "endocrine" and non-ventilatory functions of the lungs and in the production of the airspace lining layer. BIBLIOGRAPHIC REFERENCES: Ryan, J.W., Ryan, U.S., Schultz, D.R., Whitaker, C., Chung, A. and Dorer, F.E.: Subcellular localization of pulonary angiotensin converting enzyme (kininase II). Biochem. J., 146:497-499, 1975. Ryan, U.S., Ryan, J.W., Smith, D.S. and Winkler, H.: Fenestrated endothelium of the adrenal gland: Freeze-fracture studies. Tissue & Cell, 7:181-190, 1975.